Chronic pain has a tremendous impact on individual patients, their families, and society. Functional magnetic resonance imaging (fMRI) has been used to investigate nociceptive processing and central sensitization in the brain to better understand, and to ultimately develop improved therapies for chronic pain. The spinal cord is important in the processing of nociception, and direct animal and indirect psychophysical and behavioral human studies have demonstrated its role in the generation and maintenance of hyperalgesia and allodynia. Our overall goals are to use human spinal fMRI to elucidate mechanisms of nociceptive processing and spinal cord plasticity in healthy subjects and patients with chronic neuropathic pain. Our Hypotheses are that: (1) increases in noxious thermal stimuli will produce a corresponding increase in fMRI signal activation in the human spinal dorsal horn and increases in spatial and rostrocaudal activity; (2) a thermal-capsaicin induced experimental allodynia/hyperalgesia model and (3) chronic upper extremity neuropathic pain will result in increased spinal dorsal horn activity to non-noxious mechanical stimuli with increased rostrocaudal and spatial activity compared to the unaffected side. Specific AIMS: (1) optimize human spinal fMRI by characterizing the hemodynamic impulse response function; (2) characterize spinal cord activity (fMRI signal and spatial activation properties) in response to noxious thermal stimuli and compare to non-noxious mechanical and thermal stimuli; (3) elucidate the response of the human spinal cord to a heat/capsaicin pain model of allodynia and hyperalgesia in response to normally non-noxious mechanical stimuli; (4) characterize dorsal horn responsiveness to normally non- noxious thermal and tactile stimuli in patients with chronic neuropathic pain. We also plan to compare spinal fMRI activation patterns from noxious thermal stimuli in healthy subjects with normally non-noxious but painfully perceived thermal stimuli in chronic neuropathic pain patients. This will provide further insight into mechanisms of spinal plasticity in chronic neuropathic pain. Significance: These studies will advance our understanding of nociceptive processing in the human spinal cord and the effects of neural plasticity in experimental pain models and chronic neuropathic pain. This will enhance our knowledge of how chronic pain states are generated, maintained, and potentially treated. Furthermore, we will have a more objective means of assessing neural function in patients with peripheral nerve and spinal cord injury. [unreadable] [unreadable]